View Clinical Trial (Medical Research Study)
Inflammation and Insulin Resistance in PAD
| City: |
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Boston |
| State: |
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Massachusetts |
| Zip Code: |
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02115 |
| Conditions: |
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Cardiovascular Diseases - Peripheral Artery Disease - Inflammation - Insulin Resistance |
| Purpose: |
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This study will test the hypothesis that inflammation and insulin resistance contribute to
reduced walking distance in patients with intermittent claudication (IC) by impairing
vascular reactivity and skeletal muscle metabolic function.
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| Study Summary: |
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BACKGROUND:
Patients with peripheral artery disease (PAD) frequently have functional limitations and
symptoms of claudication that impact adversely on their quality of life. Some patients
progress to critical limb ischemia and require revascularization. Vascular inflammation and
insulin resistance are two important and interdependent conditions that are associated with
atherosclerosis. Moreover, both inflammation and insulin resistance cause abnormalities in
vascular function, and insulin resistance interferes with skeletal muscle metabolism.
Therefore, inflammation and insulin resistance provide attractive targets for therapy that
could potentially ameliorate the development of symptomatic PAD or improve the function and
clinical outcomes of patients with PAD. This study will determine whether inflammation and
insulin resistance contribute to the functional and clinical consequences of PAD.
DESIGN NARRATIVE:
This study will test the hypothesis that inflammation and insulin resistance contribute to
reduced walking distance in patients with IC by impairing vascular reactivity and skeletal
muscle metabolic function. Pain-free and maximum treadmill walking time will be measured
before and after 12 weeks of treatment with pioglitazone, atorvastatin, or placebo in a 2
times 2 factorial design protocol. Endothelium-dependent and independent vasodilation
(assessed by vascular ultrasonography), and plasma markers of inflammation and insulin
resistance will also be measured before and after drug intervention. A sub-set of patients
may opt to participate in a sub-study of skeletal muscle glucose utilization, assessed (by
[18F] fluorodeoxyglucose [FDG] positron emission tomography[PET]).
A separate group of patients with PAD scheduled to undergo elective percutaneous
revascularization will be enrolled, and will undergo pre- and post-intervention FDG/PET
scanning, to ascertain whether skeletal muscle glucose utilization changes with anticipated
improvements in blood flow following intervention.
Patients will be recruited from the vascular medicine, surgery, and cardiology clinics at
Brigham and Women's Hospital. All study visits take place in the Vascular Medicine Research
Center. After two preliminary visits, patients are randomized to one of four drug
interventions. Outcome measurements of the study will include insulin resistance, skeletal
muscle glucose utilization by PET, systemic inflammatory markers, circulating and local
adipocyte markers of peroxisome proliferator-activated receptor (PPAR) activation, in vivo
vascular function by ultrasonography, ankle/brachial index (ABI), and treadmill walking
time.
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| Criteria: |
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Inclusion Criteria:
- IC group inclusion criteria are as follows:
1. Lower extremity PAD and IC
2. Stable IC (as defined by the San Diego Claudication Questionnaire) for at least
6 months prior to study entry
3. Resting ABI of less than or equal to 0.90
4. Maximal walking time (MWT) between 1 and 20 minutes and post-exercise ABI drop
by greater than or equal to 20% (as measured by an exercise treadmill test at
the baseline visit, with assessment of pain free walking time [PFWT], MWT, and
measurement of the ABI in the index [most symptomatic] leg within 1 minute of
concluding exercise)
- Revascularization group inclusion criteria are as follows:
1. PAD
2. Scheduled to undergo lower extremity percutaneous revascularization
- Control group participants will have no known medical problems and a normal
cardiovascular exam
Exclusion Criteria:
- Myocardial infarction or coronary artery bypass surgery within 6 months prior to
study entry
- Transient ischemic attack or ischemic stroke 6 months prior to study entry
- Pregnancy
- Uncontrolled hypertension, defined as a systolic pressure greater than 180 mm Hg
and/or diastolic pressure greater than 100 mm Hg
- Serum creatinine greater than 2.5
- Hepatic transaminases greater than 3 times upper limit of normal
- Creatine kinase greater than 5 times upper limit of normal
- IC group exclusion criteria are as follows:
1. Must discontinue treadmill exercise for reasons other than muscular leg pain
(e.g., shortness of breath, chest pain, back pain)
2. Type 1 or insulin-dependent Type 2 diabetes
3. Lower extremity revascularization (surgical or percutaneous intervention) within
6 months prior to study entry
4. Fasting glucose greater than 110 mg/dL
5. Hypersensitivity to HMG-CoA reductase inhibitors
6. Low-density lipoprotein levels greater than 190 mg/dL, after HMG-CoA reductase
inhibitors discontinuation (patients treated with HMG-CoA reductase inhibitors
[statins] must discontinue therapy for 4 weeks prior to the baseline screening
visit, and remain off treatment throughout the study [maximum of 15 weeks])
- Revascularization group will exclude patients with an active infection
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| NCT ID: |
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NCT00225940 |
| Primary Contact: |
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Principal Investigator
Mark A. Creager
Brigham and Women's Hospital
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| Backup Contact: |
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N/A |
| Location Contact: |
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Boston, Massachusetts 02115
United States
Jeanne Doyle, RN
Phone: 617-525-7055
Email: jdoyle7@partners.org
Site Status: Recruiting |
| Data Source: |
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ClinicalTrials.gov |
| Date Processed: |
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May 25, 2013 |
| Modifications to this listing: |
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